title: Bone morphogenetic protein-2 gene controls tooth root development in coordination with formation of the periodontium.
abstract: Formation of the periodontium begins following onset of tooth-root formation in a coordinated manner after birth. Dental follicle progenitor cells are thought to form the cementum, alveolar bone and Sharpey's fibers of the periodontal ligament (PDL). However, little is known about the regulatory morphogens that control differentiation and function of these progenitor cells, as well as the progenitor cells involved in crown and root formation. We investigated the role of bone morphogenetic protein-2 (Bmp2) in these processes by the conditional removal of the Bmp2 gene using the Sp7-Cre-EGFP mouse model. Sp7-Cre-EGFP first becomes active at E18 in the first molar, with robust Cre activity at postnatal day 0 (P0), followed by Cre activity in the second molar, which occurs after P0. There is robust Cre activity in the periodontium and third molars by 2 weeks of age. When the Bmp2 gene is removed from Sp7(+) (Osterix(+)) cells, major defects are noted in root, cellular cementum and periodontium formation. First, there are major cell autonomous defects in root-odontoblast terminal differentiation. Second, there are major alterations in formation of the PDLs and cellular cementum, correlated with decreased nuclear factor IC (Nfic), periostin and α-SMA(+) cells. Third, there is a failure to produce vascular endothelial growth factor A (VEGF-A) in the periodontium and the pulp leading to decreased formation of the microvascular and associated candidate stem cells in the Bmp2-cKO(Sp7-Cre-EGFP). Fourth, ameloblast function and enamel formation are indirectly altered in the Bmp2-cKO(Sp7-Cre-EGFP). These data demonstrate that the Bmp2 gene has complex roles in postnatal tooth development and periodontium formation.
authors.affiliation: Department of Periodontics, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Audrey
authors.initials: A
authors.lastname: Rakian
authors.forename: Wu-Chen
authors.initials: WC
authors.lastname: Yang
authors.forename: Jelica
authors.initials: J
authors.lastname: Gluhak-Heinrich
authors.forename: Yong
authors.initials: Y
authors.lastname: Cui
authors.forename: Marie A
authors.initials: MA
authors.lastname: Harris
authors.forename: Demitri
authors.initials: D
authors.lastname: Villarreal
authors.forename: Jerry Q
authors.initials: JQ
authors.lastname: Feng
authors.forename: Mary
authors.initials: M
authors.lastname: Macdougall
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Harris
mesh_terms: D000199:Actins / Q000032:analysis; D051698:Activating Transcription Factor 2 / Q000235:genetics; D000367:Age Factors; D000565:Ameloblasts / Q000473:pathology; D000566:Amelogenesis / Q000235:genetics; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000032:analysis; D002454:Cell Differentiation / Q000235:genetics; D025021:Cementogenesis / Q000235:genetics; D003739:Dental Cementum / Q000473:pathology; D003782:Dental Pulp / Q000098:blood supply; D005456:Fluorescent Dyes; D049452:Green Fluorescent Proteins; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D055806:Microvessels / Q000473:pathology; D008963:Molar / Q000254:growth & development; D008964:Molar, Third / Q000254:growth & development; D051839:NFI Transcription Factors / Q000032:analysis; D009804:Odontoblasts / Q000473:pathology; D009805:Odontogenesis / Q000235:genetics*; D010513:Periodontal Ligament / Q000254:growth & development*; D000076182:Sp7 Transcription Factor; D013234:Stem Cells / Q000502:physiology; D014092:Tooth Root / Q000254:growth & development*; D014157:Transcription Factors / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D016335:Zinc Fingers / Q000235:genetics
chemical_list: D000199:Actins; D051698:Activating Transcription Factor 2; C497106:Atf2 protein, mouse; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D015815:Cell Adhesion Molecules; D005456:Fluorescent Dyes; D051839:NFI Transcription Factors; C497648:Nfic protein, mouse; C082838:Postn protein, mouse; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; C544013:alpha-smooth muscle actin, mouse; C485184:enhanced green fluorescent protein; C467480:vascular endothelial growth factor A, mouse; D049452:Green Fluorescent Proteins